Prof. Nathan Dascal

Professor, Department of Physiology and Pharmacology, Sackler School of Medicine

 

Education

1969-1974	B.Sc., Faculty of Biology	University of Leningrad (USSR)
1975-1977	M.Sc. with distinction, Department of Physiology and Pharmacology	Tel Aviv University
1979-1983	Ph.D., Department of Physiology and Pharmacology	Tel Aviv University

 

Signal Transduction by Neurotransmitters in Brain and Heart in Health and Disease

Electrical activity of excitable cells is their most important feature, which allows the performance of fundamental functions of brain, heart and muscle. We are addressing a key issue in modern cardiology and neurobiology: how neurotransmitters regulate cardiac cells and neurons by acting on ion channels – proteins that underlie the electrical activity in these cells; and how errors in these processes cause disease.

• Main projects in the lab include: Function and regulation of receptors, G proteins, Ca2+ and K+ channels in health and disease; Ion channel-related hereditary cardiac and neurological disorders (channelopathies); Mechanisms of coupling of G protein-coupled receptors with effectors; Molecular mechanisms of bipolar disorder.
• Research methods: Electrophysiology, Neurophysiology, Heterologous Expression, Protein Biochemistry, Fluorescence Resonance Energy Transfer (FRET), Molecular biology, Mathematical and Kinetic Modeling and Simulation, Immunocytochemistry

 

Publications

Babai N, Kanevsky N, Dascal N, Rozanski GJ, Singh DP, Fatma N &Thoreson WB (2010). Anion sensitive regions of L-type CaV1.2 calcium channels expressed in HEK293 cells. PLoS One, 5, e8602.

 

Berlin S, Keren-Raifman T, Castel R, Rubinstein M, Dessauer CW, Ivanina T & Dascal N (2010). Gαi and Gβγ jointly regulate the conformations of a Gβγ effector, the neuronal G-protein activated K+ channel (GIRK). J Biol Chem, 285, 6179-6185.

 

Edelheit O, Hanukoglu I, Shriki Y, Tfilin M, Dascal N, Gillis D & Hanukoglu A (2010). Truncated β epithelial sodium channel (ENaC) subunits responsible for multi-system pseudohypoaldosteronism support partial activity of ENaC. J Steroid Biochem Mol Biol, 119, 84-88.

 

Tselniker I, Tsemakhovich VA, Dessauer CW & Dascal N. (2010) Stargazin modulates neuronal voltage-dependent Ca2+ channel CaV2.2 by a Gβγ-dependent mechanism. J Biol Chem 285, 20462-20471.

 

Laish-Farkash A, Brass D, Marek-Yagel D, Pras E, Dascal N, Antzelevitch C, Nof E, Reznik H, Glikson M & Luria D (2010). A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews. J Cardiovasc Electrophysiol 21, 1365-1372.

 

Tselnicker I & Dascal N. (2010). Further characterization of regulation of CaV2.2 by stargazin. Channels 4, 351-354.

 

Oz S, Tsemakhovich V, Christel CJ, Lee A & Dascal N. (2011). CaBP1 regulates voltage dependent inactivation and activation of CaV1.2 (L-type) calcium channels. J Biol Chem 286, 13945-13953.

 

Edelheit O, Hanukoglu I, Dascal N & Hanukoglu A. (2011) Identification of the roles of conserved charged residues in the extracellular domain of an epithelial sodium channel (ENaC) subunit by alanine mutagenesis. Am J Physiol Renal Physiol 300, F887-897.

 

Berlin S, Tsemakhovich VA, Castel R, Ivanina T, Dessauer CW, Keren-Raifman T & Dascal N. (2011) Two distinct aspects of coupling between Gαi and G protein-activated K+ channel (GIRK) revealed by fluorescently-labeled Gαi3 subunits. J Biol Chem 287, 19537-19549.

 

Almagor L, Chomsky-Hecht O, Ben-Mocha A, Hendin-Barak D, Dascal N & Hirsch JA. (2012). The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis. J Neurosci 32, 7602-7613.

 

Pankonien I, Otto A, Dascal N, Morano I & Haase H. (2012). Ahnak1 interaction is affected by phosphorylation of Ser-296 on CaVβ2. Biochem Biophys Res Commun 421, 184-189.

 

Weiss S, Keren-Raifman T, Oz S, Ben Mocha A, Haase H & Dascal N. (2012). Modulation of distinct isoforms of L-type calcium channels by Gq-coupled receptors in Xenopus oocytes: Antagonistic effects of Gβγ and protein kinase C. Channels 6, 426-437.

 

Almagor L, Chomsky-Hecht O, Ben Mocha A, Hendin-Barak D, Dascal N & Hirsch JA. (2012). CaV1.2 I-II linker structure and Timothy syndrome. Channels 6, 468-472.

 

Edvardson S, Oz S, Abulhijaa FA, Taher FB, Shaag A, Zenvirt S, Dascal N & Elpeleg O. (2013). Early infantile epileptic encephalopathy associated with a high voltage-gated calcium channelopathy. J Med Genet 50, 118-123

 

Treiber F, Rosker C, Keren-Raifman T, Steinecker B, Gorischek A, Dascal N & Schreibmayer W. (2013) Molecular basis of the facilitation of the heterooligomeric GIRK1/GIRK4 complex by cAMP dependent protein kinase. Biochim Biophys Acta 1828, 1214-1221.

 

Oz S, Benmocha A, Sasson Y, Sachyani D, Almagor L, Lee A, Hirsch JA & Dascal N. (2013). Competitive and non-competitive regulation of calcium-dependent inactivation in CaV1.2 L-type Ca2+ channels by calmodulin and Ca2+-binding protein 1. J Biol Chem. 288, 12680-12691.

 

Weisbrod, D., Peretz, A., Ziskind, A., Menaker, N., Oz, S., Barad, L., Eliyahu, S., Itskovitz-Eldor, J., Dascal, N., Khananshvili, D., Binah, O., and Attali, B. (2013) SK4 Ca2+ activated K+ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells. Proc Natl Acad Sci USA 110, E1685-1694.

 

Farhy Tselnicker I, Tsemakhovich V, Rishal I, Kahanovitch U, Dessauer CW & Dascal N. (2014). Dual regulation of G proteins and the G-protein–activated K+ channels by lithium. Proc Natl Acad Sci USA 111, 5018-5023.

 

Edelheit O, Ben-Shahar R, Dascal N, Hanukoglu A & Hanukoglu I. (2014). Conserved charged residues at the surface and interface of epithelial sodium channel (ENaC) subunits: roles in cell surface expression and Na+ self-inhibition response. FEBS J. 281:2097-111.

 

Kahanovitch U, Tsemakhovich V, Berlin S, Rubinstein M, Styr B, Castel R, Peleg S, Tabak G, Dessauer CW, Ivanina T & Dascal N (2014) Recruitment of Gβγ controls the basal activity of GIRK channels: crucial role of distal C-terminus of GIRK1. J Physiol London. 592, 5373-5390

 

Yakubovich D, Berlin S, Kahanovitch U, Rubinstein M, Farhy Tselnicker I, Styr B, Keren-Raifman T, Dessauer CW & Dascal N. A quantitative model of the GIRK1/2 channel reveals that its basal and evoked activities are controlled by unequal stoichiometry of Gα and Gβγ. PLoS Comput Biol accepted for publication.

 

Benmocha Guggenheimer A, Almagor L, Tsemakhovich V, Tripathy DR, Hirsch JA & Dascal N. (Interactions between N and C termini of α1C subunit regulate inactivation of CaV1.2 L-type Ca2+ channel. Channels (Austin). 2016;10:55-68.

 

Oz S, Pankonien I, Belkacemi A, Flockerzi V, Klussmann E, Haase H & Dascal N. (2017). Protein kinase A regulates C-terminally truncated CaV1.2 in Xenopus oocytes: roles of N- and C-termini of the α1C subunit. J Physiol London, 595, 3181–3202.

 

Kahanovitch U, Berlin S & Dascal N. (2017) Collision coupling in the GABAB receptor - G protein - GIRK signaling cascade. FEBS Lett 591, 2816-2825
Dascal N & Rubinstein M. (2017) Lithium reduces the span of G protein-activated K+ (GIRK) channels inhibition in hippocampal neurons. Bipolar Disord, in press. DOI: 10.1111/bdi.12536.

 

Keren Raifman T, Kumar P, Haase H, Klussmann E, Dascal N & Weiss S. (2017) Protein kinase C enhances plasma membrane expression of cardiac L-type calcium channel, CaV1.2. Channels (Austin), 1-12. 

 

 

Reviews

Weiss S, Oz S, Benmocha A, Dascal N. (2013) Regulation of cardiac L-type Ca2+ channel CaV1.2 via the β-adrenergic-cAMP-protein kinase A pathway: old dogmas, advances, and new uncertainties. Circ Res 2013, 113:617-31.

 

Dascal N & Kahanovitch U. (2015) The roles of Gβγ and Gα in gating and regulation of GIRK channels. Int Rev Neurobiol 123, 27-85.

 

Weiss S & Dascal N. (2015) Molecular aspects of modulation of L-type calcium channels by protein kinase C. Curr Mol Pharmacol 8, 43-53.